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1

De Martinis, Massimo, Lia Ginaldi, Maria Maddalena Sirufo, et al. "Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review." Medicina 56, no. 3 (2020): 138. http://dx.doi.org/10.3390/medicina56030138.

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Alarmins are endogenous mediators released by cells following insults or cell death to alert the host’s innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiolo
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Lu, Huijiao, Mengyi Zhu, Lin Qu, Hongwei Shao, Rongxin Zhang, and Yan Li. "Oncogenic Role of HMGB1 as an Alarming in Robust Prediction of Immunotherapy Response in Colorectal Cancer." Cancers 14, no. 19 (2022): 4875. http://dx.doi.org/10.3390/cancers14194875.

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Objective: To assess the correlation between HMGB1 expression and the patient prognosis in a multicancer context. Methods: The potential oncogenic role of HMGB1 was explored in forty tumors through the TCGA, GEO, and Oncomine datasets. We analyzed the clinical prognostic value and antitumor immunotherapy of HMGB1 in a multicancer context using GEO (GSE111636). Results: High expression of HMGB1 is present in multicancer cases, and its low expression is closely associated with the prognostic survival of patients, in terms of both overall and disease-free survival in ACC and LUAD. Further investi
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Palumbo, Antonino, Fabiola Atzeni, Giuseppe Murdaca, and Sebastiano Gangemi. "The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33." International Journal of Molecular Sciences 24, no. 15 (2023): 12143. http://dx.doi.org/10.3390/ijms241512143.

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Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the largest disability problem worldwide. Recent findings have described the role of damage-associated molecular patterns (DAMPs) in the course of the disease. In particular, alarmins such as HMGB1, IL-33, and S100B, appear implicated in enhancing articular inflammation and favouring a catabolic switch in OA chondrocytes. The aims of this review are to clarify the molecular signalling of these three molecules in OA pathogenesis, t
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4

Casciaro, Marco, Eleonora Di Salvo, and Sebastiano Gangemi. "HMGB-1 in Psoriasis." Biomolecules 12, no. 1 (2021): 60. http://dx.doi.org/10.3390/biom12010060.

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Psoriasis is a multifactorial pathology linked to systemic inflammation. Enhanced keratinocytes proliferation and a minor maturation state of the cells are typical features. Perivascular T cells, dendritic cells, macrophages, and neutrophilic granulocytes are part of the scenario completed by apoptosis dysregulation. Several proinflammatory mediators, alarmins and growth factors are increased too, both in the skin and the patients’ blood. HMGB1 is important as an alarmin in several inflammatory conditions. Released after cellular damage, HMGB1 acts as a danger signal. Several studies have cons
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5

Yang, De, Yuri V. Postnikov, Yana Li, et al. "High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharide-induced immune responses." Journal of Experimental Medicine 209, no. 1 (2011): 157–71. http://dx.doi.org/10.1084/jem.20101354.

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Alarmins are endogenous mediators capable of promoting the recruitment and activation of antigen-presenting cells (APCs), including dendritic cells (DCs), that can potentially alert host defense against danger signals. However, the relevance of alarmins to the induction of adaptive immune responses remains to be demonstrated. In this study, we report the identification of HMGN1 (high-mobility group nucleosome-binding protein 1) as a novel alarmin and demonstrate that it contributes to the induction of antigen-specific immune responses. HMGN1 induced DC maturation via TLR4 (Toll-like receptor 4
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6

Jiang, Lili, Yijia Shao, Yao Tian, Changsheng Ouyang, and Xiaohua Wang. "Nuclear Alarmin Cytokines in Inflammation." Journal of Immunology Research 2020 (December 4, 2020): 1–8. http://dx.doi.org/10.1155/2020/7206451.

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Pathogen-associated molecular patterns (PAMPs) are some nonspecific and highly conserved molecular structures of exogenous specific microbial pathogens, whose products can be recognized by pattern recognition receptor (PRR) on innate immune cells and induce an inflammatory response. Under physiological stress, activated or damaged cells might release some endogenous proteins that can also bind to PRR and cause a harmful aseptic inflammatory response. These endogenous proteins were named damage-associated molecular patterns (DAMPs) or alarmins. Indeed, alarmins can also play a beneficial role i
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7

Briquet, Sylvie, Nadou Lawson-Hogban, Bertrand Boisson, et al. "Disruption of Parasitehmgb2Gene Attenuates Plasmodium berghei ANKA Pathogenicity." Infection and Immunity 83, no. 7 (2015): 2771–84. http://dx.doi.org/10.1128/iai.03129-14.

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Eukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that thePlasmodiumgenome encodes two genuine HMGB factors,PlasmodiumHMGB1 and HMGB2, that encompass, like their human counterparts, a proinflammatory domain. Given that these proteins are released from parasitized red blood cells, we then hypothesized thatPlasmodiumHMGB migh
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8

Bidwell, Joseph P., Jieping Yang, and Alexander G. Robling. "Is HMGB1 an osteocyte alarmin?" Journal of Cellular Biochemistry 103, no. 6 (2008): 1671–80. http://dx.doi.org/10.1002/jcb.21572.

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Yang, De, Yuri Postnikov, Yana Li, et al. "High mobility group nucleosome-binding protein 1 acts as an alarmin critical for the induction of immune response (113.7)." Journal of Immunology 186, no. 1_Supplement (2011): 113.7. http://dx.doi.org/10.4049/jimmunol.186.supp.113.7.

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Abstract Alarmins, defined as endogenous mediator(s) capable of promoting the recruitment and activation of antigen-presenting cells (APCs) including dendritic cells (DCs), can potentially promote immunity, however, their essential contribution to the induction immune responses remain to be demonstrated. Here we report the identification of HMGN1 as a novel alarmin that is critical to the induction of antigen-specific immune response. HMGN1 induced DC maturation and recruitment of APCs and activated NF-κB and multiple MAPKs, in a MyD88-dependent manner. HMGN1 promoted antigen-specific immune r
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10

Mezentsev, A. V., E. V. Denisova, V. V. Sobolev, and I. M. Korsunskaya. "The role of alarmins in the pathogenesis of psoriasis." Meditsinskiy sovet = Medical Council, no. 14 (September 28, 2023): 62–70. http://dx.doi.org/10.21518/ms2023-276.

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Alarmins are a group of immune activating proteins/peptides that initiate an inflammatory process by interacting with immune cells. The alarmins are biosynthesized as a result of cell injury, often due to proteolysis of native proteins. Most often, the alarmins are released into the extracellular matrix as a result of infection, burn or trauma. Several studies have been conducted recently to determine the role of alarmins in the pathogenesis of autoimmune diseases. This work was aimed to assess the clinical potential of alarmins and characterize their role in the pathogenesis of psoriasis. The
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11

Davalos, Albert R., Misako Kawahara, Gautam K. Malhotra, et al. "p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes." Journal of Cell Biology 201, no. 4 (2013): 613–29. http://dx.doi.org/10.1083/jcb.201206006.

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Cellular senescence irreversibly arrests proliferation in response to potentially oncogenic stress. Senescent cells also secrete inflammatory cytokines such as IL-6, which promote age-associated inflammation and pathology. HMGB1 (high mobility group box 1) modulates gene expression in the nucleus, but certain immune cells secrete HMGB1 as an extracellular Alarmin to signal tissue damage. We show that nuclear HMGB1 relocalized to the extracellular milieu in senescent human and mouse cells in culture and in vivo. In contrast to cytokine secretion, HMGB1 redistribution required the p53 tumor supp
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12

Cher, Jonathon Z. B., Moeed Akbar, Susan Kitson, et al. "Alarmins in Frozen Shoulder: A Molecular Association Between Inflammation and Pain." American Journal of Sports Medicine 46, no. 3 (2017): 671–78. http://dx.doi.org/10.1177/0363546517741127.

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Background: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. Purpose: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects. Study Design: Controlled laboratory study. Methods: Shoulder capsule samples were collected from 10 patients
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13

Yuan, Kaiqiang, Hu Wang, Yingming Zhou, and Taolang Li. "The Role of Alarmins in Breast Cancer." International Journal of Biology and Life Sciences 8, no. 1 (2024): 31–40. http://dx.doi.org/10.54097/30f8ej75.

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Breast cancer (BC) remains the most common malignant tumor in women globally, with its incidence and mortality ranking first and second among female cancers, respectively. Despite continuous innovation and progress in modern medicine, current clinical treatment strategies for breast cancer still face high mortality rates. Therefore, developing new therapeutic targets and strategies is urgently needed. Alarmins are a class of endogenous molecules released during non-programmed cell death (such as infection or injury), and they typically serve as early warning signals for the immune system. Earl
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14

Borsky, Pavel, Zdenek Fiala, Ctirad Andrys, et al. "Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris." Mediators of Inflammation 2020 (April 15, 2020): 1–7. http://dx.doi.org/10.1155/2020/8465083.

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Background. Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. Objective. The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomark
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15

Strohalmová, Sabina, Kateřina Levová, Aleš Antonín Kuběna, et al. "Alarmins and Related Molecules in Elective Surgery." Folia Biologica 69, no. 2 (2023): 50–58. http://dx.doi.org/10.14712/fb2023069020050.

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Surgery is associated with alterations of alarmins’ and related molecules’ levels. The aim of this study was to investigate which biomarkers are most involved in surgery. The studied group consisted of 58 patients with inguinal or umbilical hernia or cholecystolithiasis and 21 healthy controls for compa­rison. We also added seven acute patients with appendicitis, cholecystitis and incarcerated hernia. Serum concentrations of soluble receptor of advanced glycation end-products (sRAGE), extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE), calprot
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Chung, Hyunwoo, Sol Seo, Sung Ji Hong, So Won Choi, and Chung-Gyu Park. "The alarmin HMGB1 in cell cytoplasm can modulate the apoptosis to autophagy switch of pancreatic beta cells under stress." Journal of Immunology 204, no. 1_Supplement (2020): 161.28. http://dx.doi.org/10.4049/jimmunol.204.supp.161.28.

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Abstract High mobility group box 1 (HMGB1) is an infamous alarmin which is known to be harmful to pancreatic beta cells and associated with diabetes mellitus pathogenesis and pancreatic islet graft failure. However, recent studies have indicated that cytosolic HMGB1 could function as a modulator to relieve cells from apoptotic stress by inducing autophagy. Particularly, pancreatic beta cells have been well-known to demonstrate the apoptosis to autophagy switch when exposed to hypoxia or lipoxiticy. In this study, we have investigated the beta cells under hypoxic and lipotoxic stress with CCK8
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17

WANG, ZHEN, HONG ZHOU, HUAPING ZHENG, XIU TENG, XIAOQIONG WEI, and JIONG LI. "Autophagy-based unconventional secretion of alarmin HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation." Journal of Immunology 202, no. 1_Supplement (2019): 59.1. http://dx.doi.org/10.4049/jimmunol.202.supp.59.1.

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Abstract The precise mechanism by which autophagy affects psoriasis is poorly understood. Here we show that keratinocytes (KCs) autophagy was activated in psoriatic lesions of patients and mice model, positively correlating with psoriatic severity, and could be inhibited by MAPK family (ERK, p38, JNK) inactivation, implying autophagy was associated with psoriatic inflammation. Indeed, impaired autophagy flux, caused by autophagy inhibitors or KC-specific deletion of Atg5, alleviated psoriasisform inflammation, demonstrating autophagy positively regulated psoriatic inflammation. We then found a
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18

Toia, Liana M., John Mariano, Michael Weinstein Winter, and Jessica C. Shand. "Alarmin High Mobility Group Box 1 (HMGB1) Activates Alternative NFkB Signaling in Bone Marrow Macrophages in the Leukemia Microenvironment." Blood 126, no. 23 (2015): 2204. http://dx.doi.org/10.1182/blood.v126.23.2204.2204.

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Abstract High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) that signals through pattern recognition receptors on monocyte/macrophages to recruit them to sites of tissue injury. In models of sepsis and autoimmunity, HMGB1 can have both immune-activating and regulatory effects depending on the receptor system engaged and the downstream pathway activated. Although chemotherapy-stressed tumor cells are known to release HMGB1, little is known about the effects of tumor-derived HMGB1 on macrophages in the tumor microenvironment. We have previously shown that primary h
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Fonken, Laura K., Matthew G. Frank, Meagan M. Kitt, et al. "The Alarmin HMGB1 Mediates Age-Induced Neuroinflammatory Priming." Journal of Neuroscience 36, no. 30 (2016): 7946–56. http://dx.doi.org/10.1523/jneurosci.1161-16.2016.

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Gombert, Jean-Marc, Antoine Thierry, Aurelie Robin, et al. "Study of alarmin release during ischemia reperfusion injury after human renal transplantation (P2214)." Journal of Immunology 190, no. 1_Supplement (2013): 69.45. http://dx.doi.org/10.4049/jimmunol.190.supp.69.45.

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Abstract The endogenous molecules high-mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been recognized as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to prior transplantation. Moreover, a significant correlation was shown between both serum and urinary IL-33 (but not HMGB1) levels and cold ischemia time, from 30
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21

Yang, De, Yana Li, Yingjie Nie, Anna Trivett, and Joost J. Oppenheim. "Keratinocyte Release of Alarmin HMGN1 Is triggered by Elevation of Intracellular Calcium." Journal of Immunology 196, no. 1_Supplement (2016): 203.19. http://dx.doi.org/10.4049/jimmunol.196.supp.203.19.

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Abstract Intra-nuclear high-mobility group nucleosome-binding 1 (HMGN1) functions as a chromatin modulator to regulate gene expression, whereas extracellular HMGN1 acts as an alarmin and contributes to the induction of antigen-specific immune responses. However, aside from passive release resulting from cell injury, it is unclear whether HMGN1 is released extracellularly by viable cells. In this study, we studied the cell type(s) capable of releasing HMGN1 and the underlying mechanism(s). Using a keratinocyte cell line KERTr, we found that ionomycin could induce the release of HMGN1 without ch
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Furci, Fabiana, Giuseppe Murdaca, Corrado Pelaia, et al. "TSLP and HMGB1: Inflammatory Targets and Potential Biomarkers for Precision Medicine in Asthma and COPD." Biomedicines 11, no. 2 (2023): 437. http://dx.doi.org/10.3390/biomedicines11020437.

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The airway epithelium, through pattern recognition receptors expressed transmembrane or intracellularly, acts as a first line of defense for the lungs against many environmental triggers. It is involved in the release of alarmin cytokines, which are important mediators of inflammation, with receptors widely expressed in structural cells as well as innate and adaptive immune cells. Knowledge of the role of epithelial cells in orchestrating the immune response and mediating the clearance of invading pathogens and dead/damaged cells to facilitate resolution of inflammation is necessary to underst
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Suica, Viorel I., Elena Uyy, Luminita Ivan, et al. "Cardiac Alarmins as Residual Risk Markers of Atherosclerosis under Hypolipidemic Therapy." International Journal of Molecular Sciences 23, no. 19 (2022): 11174. http://dx.doi.org/10.3390/ijms231911174.

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Increased levels of low-density lipoproteins are the main risk factor in the initiation and progression of atherosclerosis. Although statin treatment can effectively lower these levels, there is still a residual risk of cardiovascular events. We hypothesize that a specific panel of stress-sensing molecules (alarmins) could indicate the persistence of silent atherosclerosis residual risk. New Zealand White rabbits were divided into: control group (C), a group that received a high-fat diet for twelve weeks (Au), and a treated hyperlipidemic group with a lipid diet for eight weeks followed by a s
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Gangemi, Sebastiano, Marco Casciaro, Giovanni Trapani, et al. "Association between HMGB1 and COPD: A Systematic Review." Mediators of Inflammation 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/164913.

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HMGB1 is an alarmin, a protein that warns and activates inflammation. Chronic obstructive pulmonary disease (COPD) is characterised by a progressive airflow obstruction and airway inflammation. Current anti-inflammatory therapies are poorly effective in maintaining lung function and symptoms of COPD. This underlines the need for finding new molecular targets involved in disease pathogenesis in order to block pathology progression. This review aims to analyse latest advances on HMGB1 role, utilisation, and potential application in COPD. To this purpose we reviewed experimental studies that inve
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Galaz, Jose, Roberto Romero, Marcia Arenas-Hernandez, Bogdan Panaitescu, Robert Para, and Nardhy Gomez-Lopez. "Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study." Journal of Perinatal Medicine 49, no. 7 (2021): 897–906. http://dx.doi.org/10.1515/jpm-2021-0049.

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Abstract Objectives Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmin-induced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic i
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Lamkanfi, Mohamed, Anasuya Sarkar, Lieselotte Vande Walle, et al. "Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia." Journal of Immunology 185, no. 7 (2010): 4385–92. http://dx.doi.org/10.4049/jimmunol.1000803.

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Harris, Helena Erlandsson, Ulf Andersson, and David S. Pisetsky. "HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease." Nature Reviews Rheumatology 8, no. 4 (2012): 195–202. http://dx.doi.org/10.1038/nrrheum.2011.222.

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Allegra, Alessandro, Giuseppe Murdaca, Luca Gammeri, Roberta Ettari, and Sebastiano Gangemi. "Alarmins and MicroRNAs, a New Axis in the Genesis of Respiratory Diseases: Possible Therapeutic Implications." International Journal of Molecular Sciences 24, no. 2 (2023): 1783. http://dx.doi.org/10.3390/ijms24021783.

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It is well ascertained that airway inflammation has a key role in the genesis of numerous respiratory pathologies, including asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Pulmonary tissue inflammation and anti-inflammatory responses implicate an intricate relationship between local and infiltrating immune cells and structural pulmonary cells. Alarmins are endogenic proteins discharged after cell injury in the extracellular microenvironment. The purpose of our review is to highlight the alterations in respiratory diseases involving some alarmins, such a
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Ma, Huan, Ning Cheng, and Caiyi Zhang. "Schizophrenia and Alarmins." Medicina 58, no. 6 (2022): 694. http://dx.doi.org/10.3390/medicina58060694.

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Schizophrenia, consisting of a group of severe psychiatric disorders with a complex etiology, is a leading cause of disability globally. Due to the lack of objective indicators, accurate diagnosis and selection of effective treatments for schizophrenia remain challenging. The association between schizophrenia and alarmins levels has been proposed for many years, but without solid evidence. Alarmins are prestored molecules that do not require processing and can be released upon cell death or damage, making them an ideal candidate for an early initiator of inflammation. Immunological biomarkers
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Yang, De, Michael Bustin, and Joost J. Oppenheim. "Harnessing the alarmin HMGN1 for anticancer therapy." Immunotherapy 7, no. 11 (2015): 1129–31. http://dx.doi.org/10.2217/imt.15.76.

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Rabadi, May M., Mei-Chuan Kuo, Tammer Ghaly, et al. "Interaction between uric acid and HMGB1 translocation and release from endothelial cells." American Journal of Physiology-Renal Physiology 302, no. 6 (2012): F730—F741. http://dx.doi.org/10.1152/ajprenal.00520.2011.

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We aimed to investigate the potential relationship between alarmins [acting via Toll-like receptor-4 (TLR4)], uric acid (UA), and high-mobility group box-1 protein (HMGB1) during acute kidney injury. UA, which is significantly increased in the circulation following renal ischemia-reperfusion injury (IRI), was used both in vitro and in vivo as an early response-signaling molecule to determine its ability to induce the secretion of HMGB1 from endothelial cells. Treatment of human umbilical vein endothelial cells (HUVEC) with UA resulted in increased HMGB1 mRNA expression, acetylation of nuclear
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shi, guilan, Kennady Abbott, Russell D. Salter та Peter A. Keyel. "Inflammasome dependent IL-1β secretion requires Dnase1L3 activity". Journal of Immunology 196, № 1_Supplement (2016): 62.14. http://dx.doi.org/10.4049/jimmunol.196.supp.62.14.

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Abstract Inflammation is driven by inflammatory cell death and the secretion of pro-inflammatory cytokines like IL-1β and alarmins like High Mobility Group Box Protein 1 (HMGB1) by the inflammasome. The inflammasome is a cytosolic multiprotein complex that typically contains a Nod-like receptor (NLR), like NLRP3 or NLRC4, and the adaptor ASC which links to caspase-1 for activation. How signals from the cytoplasmic NLR induce nuclear ASC and HMGB1 translocation into the cytosol for inflammasome function remains elusive. Here we hypothesize that Dnase1L3 (DNase γ), a Ca2+/Mg2+-dependent endonucl
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Garcia-Flores, Valeria, Zhenjie Liu, Roberto Romero, et al. "M2-polarized macrophages prevent preterm birth and improve neonatal survival and immunity." Journal of Immunology 212, no. 1_Supplement (2024): 0355_5259. http://dx.doi.org/10.4049/jimmunol.212.supp.0355.5259.

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Abstract Preterm birth (PTB), commonly preceded by preterm labor, is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm labor are associated with sterile intra-amniotic inflammation (SIAI), an inflammatory condition without detectable microorganisms. To date, no successful strategies to treat SIAI have been developed. Herein, we present mechanistic proof that treatment with M2-polarized macrophages (M2 MΦ) can effectively prevent PTB [(HMGB1, n = 28 vs. HMGB1+M2 MΦ, n = 29) (p<0.05)] and neonatal mortality [(HMGB1, n = 20 litters vs. HMGB1+M2 MΦ, n =
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Parker, Katherine, Lucas Horn, Virginia Clements, et al. "Inhibition of HMGB1 delays tumor progression, reduces MDSC-mediated immune suppression, and diminishes MDSC-macrophage cross-talk (P2001)." Journal of Immunology 190, no. 1_Supplement (2013): 53.1. http://dx.doi.org/10.4049/jimmunol.190.supp.53.1.

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Abstract Tumor-induced immune suppression is driven by immune suppressive cells including Myeloid-Derived Suppressor Cells (MDSC). MDSC are present in most patients with cancer. They block T cell activation and drive type 2 immunity. Cross-talk with macrophages enhances MDSC secretion of pro-tumor molecules such as IL-10 and decreases macrophage production of IL-12. Because the alarmin HMGB1 is increased in many cancers, we are determining if HMGB1 drives MDSC. Treatment of BALB/c mice with 4T1 mammary carcinoma with HMGB1 inhibitors Glycyrrhizin or Ethyl Pyruvate reduced lung metastases, whil
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Holmannová, Drahomíra, Barbora Císařová, Pavel Borský, et al. "Goeckerman Regimen Reduces Alarmin Levels and PASI Score in Paediatric Patients with Psoriasis." Acta Medica (Hradec Kralove, Czech Republic) 64, no. 4 (2021): 204–12. http://dx.doi.org/10.14712/18059694.2022.3.

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Background. Psoriasis is a chronic systemic inflammatory disease with (extra-)cutaneous manifestations. Inflammation is associated with cellular stress and tissue damage which lead to the release of alarmins (signals of danger). Goeckerman regimen (GR) is a highly efficacious treatment consisting of the application of pharmaceutical crude tar and UVB light exposure. The reduction of inflammatory processes in the skin is accompanied by changes in the levels of inflammatory markers - alarmins (HMBG-1, S100A7, S1000A8, S100A9, S100A12, IL-17, IL-22, and IL-33). Methods. The alarmin levels in sera
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Karagyozov, Luchezar, and Jordana Todorova. "Computational Analysis of the Messenger RNA Variants Encoding Two Isoforms of the High-mobility Group box 1 Protein." Natural Science and Advanced Technology Education 30, no. 3 (2021): 243–52. http://dx.doi.org/10.53656/nat2021-3.02.

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High-mobility group box 1 protein (HMGB1) is a multifunctional nonhistone chromosomal protein. This widespread nuclear protein has a dual function-in the nucleus - it binds DNA and participates in practically all DNA-dependent processes. On the other hand, the protein plays an important role in the extracellular matrix as an “alarmin”, which interacts with certain receptors and stimulates biochemical pathways, associated with carcinogenesis and metastasis. HMGB1 is a critical damage-associated molecular pattern molecule, has been implicated in several inflammatory diseases and cancer types. Th
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Światły, Agata, Norbert Wąsik, Joanna Hajduk, et al. "Mass spectrometry analysis of redox forms of High-Mobility Group Box-1 Protein in cerebrospinal fluid: initial experience." Journal of Medical Science 88, no. 3 (2019): 171–76. http://dx.doi.org/10.20883/jms.311.

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Introduction. High-mobility group box 1 (HMGB1) is an alarmin with proinflammatory potential determined by redox status of the cysteines at position 23 and 45. It may also play a role as a biomarker in biological fluids. The aim of this study was the identification of different HMGB1 redox forms in cerebrospinal fluid (CSF) obtained from subarachnoid hemorrhage patients.
 Material and Methods. 6 CSF samples were collected from aneurysmal subarachnoid haemorrhage patients. Commercially available HMGB1 isoforms served as a positive control. Immunoprecipitation and electrophoretic isolation
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Taverna, Simona, Alessandro Tonacci, Maria Ferraro, et al. "High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases." Cells 11, no. 5 (2022): 849. http://dx.doi.org/10.3390/cells11050849.

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In the early 1970s, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and named high-mobility group (HMG) proteins. High-mobility group box 1 (HMGB1) is the most studied HMG protein that detects and coordinates cellular stress response. The biological function of HMGB1 depends on its subcellular localization and expression. It plays a critical role in the nucleus and cytoplasm as DNA chaperone, chromosome gatekeeper, autophagy maintainer, and protector from apoptotic cell death. HMGB1 also functions as an extracellular alarmin acting as a damage-associat
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Bode, Michael, David Haenel, Christoph E. Hagemeyer, et al. "HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi." Thrombosis and Haemostasis 114, no. 11 (2015): 994–1003. http://dx.doi.org/10.1160/th14-12-1073.

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SummaryHigh mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates gene expression, as well as a pro-inflammatory alarmin that is released from necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic plaques was identified. Therapeutic blockade of HMGB1 reduced the development of diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1 to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated human platelets (MFI 2.49 vs 25.01, p=
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Arnold, Edward A., Robin J. Kaai, Katie Leung, et al. "Adenovirus protein VII binds the A-box of HMGB1 to repress interferon responses." PLOS Pathogens 19, no. 9 (2023): e1011633. http://dx.doi.org/10.1371/journal.ppat.1011633.

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Viruses hijack host proteins to promote infection and dampen host defenses. Adenovirus encodes the multifunctional protein VII that serves both to compact viral genomes inside the virion and disrupt host chromatin. Protein VII binds the abundant nuclear protein high mobility group box 1 (HMGB1) and sequesters HMGB1 in chromatin. HMGB1 is an abundant host nuclear protein that can also be released from infected cells as an alarmin to amplify inflammatory responses. By sequestering HMGB1, protein VII prevents its release, thus inhibiting downstream inflammatory signaling. However, the consequence
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Kvivik, Ingeborg, Grete Jonsson, Roald Omdal, and Cato Brede. "Sample Preparation Strategies for Antibody-Free Quantitative Analysis of High Mobility Group Box 1 Protein." Pharmaceuticals 14, no. 6 (2021): 537. http://dx.doi.org/10.3390/ph14060537.

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Sickness behavior and fatigue are induced by cerebral mechanisms involving inflammatory cytokines. High mobility group box 1 (HMGB1) is an alarmin, and a potential key player in this process. Reliable quantification methods for total HMGB1 and its redox variants must be established in order to clearly understand how it functions. Current methods pose significant challenges due to interference from other plasma proteins and autoantibodies. We aimed to develop an antibody-free sample preparation method followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to measure
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Manganelli, Valeria, Antonella Capozzi, Simona Truglia, et al. "Elevated Serum Level of HMGB1 in Patients with the Antiphospholipid Syndrome." Journal of Immunology Research 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/4570715.

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Pregnancy problems are common in patients with rheumatic disease; indeed, autoimmune disorders and autoantibodies can affect pregnancy progress and lead to maternal complications. Recent studies have highlighted a close association between HMGB1, chronic inflammation, and autoimmune diseases. Thus, in this investigation, we analyzed serum levels of HMGB1, an alarmin which plays a pivotal role in inducing and enhancing immune cell function. Sera from 30 patients with antiphospholipid syndrome (11 primary and 19 secondary APS), 35 subjects with pregnancy morbidity, and 30 healthy women were anal
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Bertheloot, Damien, та Eicke Latz. "HMGB1, IL-1α, IL-33 and S100 proteins: dual-function alarmins". Cellular & Molecular Immunology 14, № 1 (2016): 43–64. http://dx.doi.org/10.1038/cmi.2016.34.

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Sung, Mia, Mahamat Babagana, Kyu-Seon Oh, et al. "Functional macrophage chromatin landscapes depend on HMGN1/HMGN2." Journal of Immunology 204, no. 1_Supplement (2020): 69.10. http://dx.doi.org/10.4049/jimmunol.204.supp.69.10.

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Abstract The High Mobility Group (HMG) proteins are ubiquitously present in the nuclei of all vertebrate cells. HMG proteins bind dynamically to chromatin without DNA sequence specificity, and they affect DNA-dependent functions such as replication, repair, and transcription, but only in the context of chromatin. HMGs are also suggested to play an important role in the immune system. Both HMGB1 and HMGN1 can act as alarmins. HMGN proteins also affect the response of B lymphocytes to bacterial LPS stimulation. HMGN proteins are typically enriched at regulatory sites such as enhancers and promot
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Gougeon, M.-L., M.-T. Melki, and H. Saïdi. "HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells." Cell Death & Differentiation 19, no. 1 (2011): 96–106. http://dx.doi.org/10.1038/cdd.2011.134.

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Horiuchi, Takahiro, Natsumi Sakata, Yoshihiro Narumi, et al. "Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity." Journal of Biological Chemistry 292, no. 20 (2017): 8436–46. http://dx.doi.org/10.1074/jbc.m116.769380.

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Peng, Travis, Shin-Yi Du, Myoungsun Son та Betty Diamond. "HIF-1α is a negative regulator of interferon regulatory factors: Implications for interferon production by hypoxic monocytes". Proceedings of the National Academy of Sciences 118, № 26 (2021): e2106017118. http://dx.doi.org/10.1073/pnas.2106017118.

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Patients with severe COVID-19 infection exhibit a low level of oxygen in affected tissue and blood. To understand the pathophysiology of COVID-19 infection, it is therefore necessary to understand cell function during hypoxia. We investigated aspects of human monocyte activation under hypoxic conditions. HMGB1 is an alarmin released by stressed cells. Under normoxic conditions, HMGB1 activates interferon regulatory factor (IRF)5 and nuclear factor-κB in monocytes, leading to expression of type I interferon (IFN) and inflammatory cytokines including tumor necrosis factor α, and interleukin 1β,
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Kondratska, O. A., N. G. Grushka, V. V. Veshko, S. I. Pavlovych, and R. I. Yanchii. "MULTIFUNCTIONAL ACTIVITY OF NUCLEAR PROTEIN AMPHOTERIN AND ITS ROLE IN ENDOTOXEMIA." Fiziolohichnyĭ zhurnal 69, no. 6 (2023): 120–32. http://dx.doi.org/10.15407/fz69.06.120.

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The review summarizes generalizing modern scientific data on the main functions of the protein HMGB1, and its physiological and pathological roles. Amphoterin is involved in key processes that ensure the functioning of DNA in the cell nucleus and plays an important role outside it. HMGB1 has been implicated in many human inflammatory diseases such as sepsis, ischemic reperfusion injury, neurological conditions, cardiovascular disease, autoimmune disease, and others. This manuscript describes the structure and main functions of HMGB1, discusses the significance of this alarmin as damage-associa
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Careccia, Giorgia, Marielle Saclier, Mario Tirone, et al. "Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy." Science Translational Medicine 13, no. 596 (2021): eaay8416. http://dx.doi.org/10.1126/scitranslmed.aay8416.

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Muscular dystrophies (MDs) are a group of genetic diseases characterized by progressive muscle wasting associated to oxidative stress and persistent inflammation. It is essential to deepen our knowledge on the mechanism connecting these two processes because current treatments for MDs have limited efficacy and/or are associated with side effects. Here, we identified the alarmin high-mobility group box 1 (HMGB1) as a functional link between oxidative stress and inflammation in MDs. The oxidation of HMGB1 cysteines switches its extracellular activities from the orchestration of tissue regenerati
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Kochi, Takahiro, Yoki Nakamura, Simeng Ma, et al. "Pretreatment with High Mobility Group Box-1 Monoclonal Antibody Prevents the Onset of Trigeminal Neuropathy in Mice with a Distal Infraorbital Nerve Chronic Constriction Injury." Molecules 26, no. 7 (2021): 2035. http://dx.doi.org/10.3390/molecules26072035.

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Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Tre
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